St. John’s wort, ursolic acid, Gardenia jasminoides

[LAJ12345]

Hubby has been having a bad patch lately with symptoms deteriorating so we decided to try increasing his madopar from 3 1/2 x 50/12.5 tablets to 5 but he couldn’t tolerate the extra (usual extra rigidity and suicidal thinking) so reduced back to 4 1/2. PD nurse still thinks it isn’t enough. Maybe with move his movement would be improved he just doesn’t tolerate it.

My guess is it’s because of his dopamine beta hydroxylase running fast, (genetic testing picked this up) breaking down the dopamine too fast so it runs out too quickly and causes rigidity and anxiety.

I looked up dopamine beta hydroxylase how to slow it down naturally and apparent st johns wort does this. So I’m trying him on a cup of this a day at the start and he seems a bit calmer but I will keep you posted over whether it is effective.

thieme-connect.com/products...

“SummaryExtracts from the herb “St. John’s wort” (Hypericum perforatum L.) are used for the treatment of mental depression, nervousness, sleeplessness and for their wound healing, diuretic and antirheumatic properties. As one biochemical mechanism for depression lack of catecholamine neurotransmitters has been discussed. The results of this investigation show that alcoholic extracts from Hypericum perforatum L. on the basis of total hypericin content inhibit dopamine - β - hydroxylase with an IC50of 0.1 µmol/l; pure commercial hypericin inhibits with an IC50 of 21 µmol/l. Enzymes involved in the synthesis of dopamine from tyrosine, namely tyrosinase and tyrosine decarboxylase, are not influenced by hypericin at concentrations from 1 up to 10 µmol/l.”

pubmed.ncbi.nlm.nih.gov/108...

” It has been recently reported that alcoholic extracts from Hypericum perforatum inhibit dopamine-beta-hydroxylase (D-beta-H) with an I50 of 0.1 mumol/l on the basis of total hypericin content and with an I50 of 21 mumol/l with pure commercial hypericin.”

chemicalbook.com/article/ap...

“recent studies report antidepressive, antineoplastic, antitumor and antiviral (human immunodeficiency and hepatitis C virus) activities of hypericin; intriguing information even if confirmation of data is incomplete and mechanisms of these activities still remain largely unexplained. In other contemporary studies, screening hypericin for inhibitory effects on various pharmaceutically important enzymes such as MAO (monoaminoxidase), PKC (protein kinase C), dopamine-beta-hydroxylase, reverse transcriptase, telomerase and CYP (cytochrome P450), has yielded results supporting therapeutic potential. Research of hypericin and its effect on GABA-activated (gamma amino butyric acid) currents and NMDA (N-methyl-D-aspartat) receptors also indicate the therapeutic potential of this substance whereby new insights in stroke research (apoplexy) are expected”

His genes analysis report is attached. Note St. John’s wort can interfere with meds so check interactions and proceed with caution

[LAJ12345]

gene test

For anyone who is interested you can get test from a natural practitioner from opus23. You need to do saliva tests and get file from ancestry.com and 23&me then the practitioner gets the test analysed and talks you through it. I would be very interested in comparing genetics of anybody who wants to and can afford to have the test done so we can see if similar symptoms and reactions to drugs occur in people with the same gene defects. Is there anyone keen to try ?

High dopamine beta hydroxylase

[Kia17 in reply to LAJ12345]

Sorry to hear that you and your husband been through all these.

Have you checked MAO A and MAO B and COMT enzymes activities in your husband genetic testing?

If MAO A is fast which I think in most of Pwpd is and dopamine and seretonin get oxidised rather too quickly. In this case low dose SSRIs can be helful (under health professionals supervision) but should not be mixed with any drugs, supplements and herbs with similar effects including St. John’s wort as mixing them can create severe reaction including seretonin syndrome.

[LAJ12345 in reply to Kia17]

they don’t mention COMT as a problem although the diagram has it shaded.

Definitely maoa and maob are brought up as an issue. They recommend excess of b2 which he has every day, vitamin d he also has. Berberine and quercetin he has had in the past but he isn’t taking now. I might try him on those again.

He has most foods on their list regularly adzuki beans,almonds,liver, dark chocolate oat bran, black beans. Lamb and milk a little.

He cannot tolerate SSRI as they make him extremely agitated and suicidal before long.

The thing they seem most concerned about is the dopamine beta hydroxylase running fast. The say it is bad outcome. And I don’t think there are Parkinson’s drugs for that. Just disulfiram for alcoholics.

The antialcoholism drug disulfiram has shown recent promise as a pharmacotherapy for treating cocaine dependence, probably via inhibition of dopamine beta-hydroxylase (DBH), the enzyme that catalyzes the conversion of dopamine (DA) to norepinephrine (NE).

He doesn’t take much else drug wise. A tiny dose of procyclidine and clonazapam in a dose doctors think should have no effect. And the tiny amount of levodopa he can barely tolerate.

They have prescribed entacapone now which is a COMT inhibitor but I’m not sure that is the right thing. 😬

I will see how St. John’s wort does first as it seems it is at least targeting the right thing

[Kia17 in reply to LAJ12345]

In my opinion vitamin B2 in this circumstance is adding fuel to the fire. B2 causes MAO A works even faster. Plus it also causes drooling. I have the fastest version of MAO A snips. I can’t take more than 20mg of b2 every few days. For people with fast MAO A, 3 meals a day that consist of protein, carbs and fats recommended as well as foods containing tryptophan.

PS: You will need to establish whether your husband’s MAO A is fast or slow. If slow then B2 is helpful.

[LAJ12345 in reply to Kia17]

I read that as it is running too slow, hence the need for b2? So an inhibitor would make it worse?

MaoB

[Kia17 in reply to LAJ12345]

You are completely right. B2 in case of slow MAO A is helpful as well as avoiding too much tryptophan.

[LAJ12345 in reply to Kia17]

how do you read the maob one? It doesn’t say if his is fast or slow does it? Comment seems general? But it does recommend the b2 as well so I’m guessing slow.

Can one be too fast and the other too slow? Can they balance each other?

I’m thinking that once upon a time his genes all balanced reasonably well for him to function so there must be pluses and minuses in areas that cancel each other out? He was always very low mood low emotion for as long as I have known him 22 years. His mother said as a little kid he refused to be hugged or show any affection. I start to wonder if he has always been a bit on the autism spectrum as he does have a lot of the manefestations when he is not feeling well. He can’t handle stimulation or noise or people etc.

[Kia17 in reply to LAJ12345]

As far as I can see from the images MAO A is slow( first line of the report indicates). It doesn’t say anything about slowness of fastness of MAO B (perhaps their SNPs database not sufficient to compare MAO B against it).

[LAJ12345 in reply to Kia17]

yes. It does say to take b2 though so implies it’s slow? Or can they offset each other?

[Kia17 in reply to LAJ12345]

Not necessarily. They have recommended a routine remedy for MAO B while they are not sure about its tendencies.

[LAJ12345 in reply to Kia17]

“Does exercise increase MAO?Those activities during and after the physical exercise have different tendency in each other enzyme. MAO-A activity was sharply decreased with stress by physical activities compared to the normal group, whereas MAO-B activity was increased for 60 minutes after exercise.”

Whaaat? Does that mean exercise can be bad?

[LAJ12345 in reply to Kia17]

fo r general reference

“Tryptophan    Tryptophan is an amino acid needed for normal growth in infants and for the production and maintenance of the body's proteins, muscles, enzymes, and neurotransmitters. It is an essential amino acid. This means your body cannot produce it, so you must get it from your diet.FunctionThe body uses tryptophan to help make melatonin and serotonin. Melatonin helps regulate the sleep-wake cycle, and serotonin is thought to help regulate appetite, sleep, mood, and pain.The liver can also use tryptophan to produce niacin (vitamin B3), which is needed for energy metabolism and DNA production. In order for tryptophan in the diet to be changed into niacin, the body needs to have enough:Iron Riboflavin Vitamin B6”

”Tryptophan can be found in:Cheese.Chicken.Egg whites.Fish.Milk.Sunflower seeds.Peanuts.Pumpkin seeds.”

[LAJ12345 in reply to Kia17]

Too slow?

Maoa

[LAJ12345 in reply to Kia17]

that’s interesting. Maybe what the other person yesterday needs for his drooling?

[Kia17 in reply to LAJ12345]

I would double check St . Johns wort with his health practitioner as it also slowing down the MAO A activity.

[LAJ12345 in reply to Kia17]

I asked PD nurse and she said fine, see if it helps, but to honest I have no faith in anything coming from that lots as they just want to try scattergun approach. They have prescribed entacapone which is COMT inhibitor for a trial. Will see if St. John’s wort works first as that seems more targeted at the dopamine beta hydroxylase . As far as I can see COMT is ok

[Kia17]

See these links; You might be able to compare your husband’s snps with them.

mygenefood.com/genes/brain-...

selfdecode.com/app/gene/maob/

wikigenes.org/e/gene/e/4129...

[LAJ12345 in reply to Kia17]

ok, thanks. I will.

[LAJ12345 in reply to LAJ12345]

”Variants of MAOB have been associated with chronic fatigue syndrome, an illness characterized by prolonged low energy. These variants may increase monoamine oxidase B activity and consequently decrease monoamine levels. Ultimately, the effects of these variants may result in a monoamine imbalance, dysregulating monoamine function [R, R]. ”

So his decreasing activity increase monoamine levels which include histamine, dopamine and seratonin? So why do they want to give him dopamine and seratonin? And does increased histamine mean allergy reactions exacerbated. Big tick there too. His hayfever as a kid was off the charts. He reckons he doesn’t have it any more but could it have just remanifested as PD symptoms?

[Kia17 in reply to LAJ12345]

He would need dopamine and seretonin for his loss of dopamine producing cells, but at the same time he should be able to get a ride of them once they have done their job. I would speak with a functional medicine to get that sorted. It’s a gray area.

[LAJ12345 in reply to Kia17]

I just don’t even know how to find such a person here. No one seems to want to do anything except try things on him for no reason except because they work on some people.

[LAJ12345 in reply to Kia17]

and how does dopamine beta hydroxylase running too fast fit into it?

[Kia17 in reply to LAJ12345]

They are managed by different enzymes and genes. For example my MAO A is fast but the COMT is wild type (normal).

[LAJ12345 in reply to Kia17]

Can they all be compensating for each other? Ie is there more than one path that can be doing the same thing? I assume when he was young they all managed to keep him stable until they went wrong.

[Kia17 in reply to LAJ12345]

I think they try to keep a balance but as long as they can afford.

All processes can be found in the Biopterin pathway. (See the screenshot).

Biopterin pathway

[LAJ12345 in reply to Kia17]

ah, thanks. That’s easier to understand how they connect than the opus23 gene one.

[LAJ12345 in reply to Kia17]

checked that first one. He has the G form of rs1798836 so it is down regulated.

For the upregulated form it says take kava kava to slow it down and he was given that for anxiety by naturopath for anxiety (duh!) and had a very negative reaction to it. So I guess proof by example that it is down regulated not upregulated.

[Kia17 in reply to LAJ12345]

In my opinion anything that reduces activity of these 3 enzymes extremely, creates more anxiety, restlessness.

[LAJ12345 in reply to Kia17]

”what is the function of COMT?COMT is an enzyme that is involved in metabolizing various catecholamine neurotransmitters, including dopamine and epinephrine. The COMT gene is 27.22kb in length, and is located on chromosome 22q11.”

So COMT also breaks down monoamines like dopamine and seratonin so if they are already too slow to break down then a COMT inhibitor would make it worse??

[Kia17 in reply to LAJ12345]

I also think the same.

[LAJ12345 in reply to Kia17]

hindawi.com/journals/bmri/2...

”AbstractMonoamine oxidase (MAO) catalyzes the oxidative deamination of amines and neurotransmitters and is involved in mood disorders, depression, oxidative stress, and adverse pharmacological reactions. This work studies the inhibition of human MAO-A by Hypericum perforatum, Peganum harmala, and Lepidium meyenii, which are reported to improve and affect mood and mental conditions. Subsequently, the antioxidant activity associated with the inhibition of MAO is determined in plant extracts for the first time. H. perforatuminhibited human MAO-A, and extracts from flowers gave the highest inhibition (IC50 of 63.6 μg/mL). Plant extracts were analyzed by HPLC-DAD-MS and contained pseudohypericin, hypericin, hyperforin, adhyperforin, hyperfirin, and flavonoids. Hyperforin did not inhibit human MAO-A and hypericin was a poor inhibitor of this isoenzyme. Quercetin and flavonoids significantly contributed to MAO-A inhibition. P. harmala seed extracts highly inhibited MAO-A (IC50 of 49.9 μg/L), being a thousand times more potent than H. perforatum extracts owing to its content of β-carboline alkaloids (harmaline and harmine). L. meyenii root (maca) extracts did not inhibit MAO-A. These plants may exert protective actions related to antioxidant effects. Results in this work show that P. harmala and H. perforatum extracts exhibit antioxidant activity associated with the inhibition of MAO (i.e., lower production of H2O2).”

Mmm, says quercetin inhibits yet they recommend it? 🧐

coffee and citrus bioflavonoids also inhibit.

[LAJ12345]

ncbi.nlm.nih.gov/pmc/articl...

”Ursolic acid exhibited significant inhibition of DBH (214 μmol/L), weak inhibition of MAO-B (780 μmol/L), and no inhibition against MAO-A. Consequently, G. jasminoides fruits are considerable for development of biofunctional food materials for the combination treatment of depression and neurodegenerative disorders.”

Maybe this is the thing for him?

Inhibits DBH and not mao.

pubmed.ncbi.nlm.nih.gov/264...

“Neuroprotective effects of geniposide in the MPTP mouse model of Parkinson's diseaseYiMei Chen 1, Yanfang Zhang 1, Lin Li 2, Christian Hölscher 3Affiliations expandPMID: 26409043 DOI: 10.1016/j.ejphar.2015.09.029Abstract

Parkinson's disease (PD) is a chronic neurodegenerative disease, and there is no cure for it at present. We tested the drug Geniposide, an active component of Gardenia jasminoides Ellis which is used in traditional Chinese medicine. Geniposide has shown neuroprotective and growth-factor like effects in several in vivo and in vitro studies. In the present study, Geniposide had been tested in an acute PD mouse model induced by four 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneal injections. Geniposide treatment (100mg/kg ip.) for 8 days after MPTP treatment (30mg/kg ip.) improved the locomotor and exploratory activity of mice (open field), and improved bradykinesia and movement balance of mice (rotarod, swim test). Geniposide treatment also restored tyrosine hydroxylase (TH) positive dopaminergic neuron numbers in the substantia nigra pars compacta. Drug treatment also increased levels of growth factor signaling molecule Bax and reduced the apoptosis signaling molecule Bcl-2. Caspase 3 activation was also reduced in the substantia nigra. We conclude that Geniposide exerted its neuroprotective effect by enhancing growth factor signaling and the reduction of apoptosis. Geniposide is an ingredient in Chinese traditional medicine with few known side effects and shows potential as a drug treatment for Parkinson's disease.”

sciencedirect.com/science/a...

”2.3. Crocin and its derivatives in G. jasminoides

Crocin and its derivatives extracted from G. jasminoides have been characterized as low toxicity, low allergy, and ecofriendly compared with saffron [3]. Crocin and crocetin were initially found in saffron, which was the dried stigma of the flower of Crocus sativus L. Saffron has a wide range of uses especially in the dye and pharmaceutical industry. It also has medicinal effects in certain conditions such as weight loss, sexual dysfunction, and premenstrual syndrome. These medicinal properties of saffron are likely attributable to a number of compounds it contains, including crocetin, crocins, and safrana”

[LAJ12345]

alzdiscovery.org/uploads/co...

What is it? Ursolic acid is a pentacyclic triterpenoid that is present in many fruits and herbs, such as apple peels, cranberry juices, grape skins, holy basil, rosemary, thyme, oregano, sage, lemon balm, marjoram, and other herbs. Ursolic acid has been studied mostly in preclinical studies for its diverse pharmacological effects including protection from cancer and neurodegenerative diseases (Habtemariam, 2019). While ursolic acid does not scavenge reactive oxygen species, it has antioxidant effects through upregulation of antioxidant defenses. It also has anti-inflammatory activities. Ursolic acid also modulates the monoaminergic system by inhibiting the monoamine oxidase A and dopamine-β hydroxylase, potentially increasing the availability of monoamines (e.g., dopamine, norepinephrine) in the synaptic cleft (Ramos-Hryb et al., 2017).

Neuroprotective Benefit: Antioxidative and anti-inflammatory effects of ursolic acid are observed in preclinical models of cognitive impairment, Alzheimer’s, Parkinson’s, brain injury, and others, but no clinical evidence in humans exist to date.

[LAJ12345 in reply to LAJ12345]

that’s odd, the other reference says it it doesn’t inhibit mao a, this says it does.

[LAJ12345]

right fruit salad with prunes an apple with peel it is!

[JeanieBeanie]

Is Sinemet not available where you are?

[LAJ12345 in reply to JeanieBeanie]

he has madopar. They started him on sinemet then changed it to Kinson as a generic for some reason, probably was cheap, which was terrible, then madopar. He tried Madopar HBS which nearly killed him, and back on the 50/12.5 tablets x 4 1/2. He tried 5 and it made him worse. Actually now on the 4 1/2 which he increased to a week ago from 3 1/2 he is worse than before he increased. It just doesn’t suit him.

[Bolt_Upright]

You are such a fighter! Good job you!

[LAJ12345 in reply to Bolt_Upright]

doesn’t seem to be helping at the moment. Can’t find the sweet spot at the moment

[LagLag37 in reply to LAJ12345]

Do you ever think that he’s taking too many supplements & meds? I’ve found that a lot of times that “less is more”. But I understand, everyone is different.

Like Bolt mentioned, you are a fighter! Your husband has a great “corner-woman” ! 🥊

[LAJ12345 in reply to LagLag37]

yes I’ve thought that and have reduced or stopped some but it never helped and he felt worse so inevitably I have started them again. They are almost all vitamins, omega 3 oils .

I actually think the same when I see the lists of medications some people are on!

[LAJ12345]

it is now 5 months later and he has been feeling much better for a few months.

Things we did:

He now takes 1/2 an entacapone with the first 3 madopar of the day, and a NOW mucuna.

He takes

6am. 1/2 madopar 50/12.5 + NOW dopa mucuna + 1/2 entacapone

8am. 1 madopar 50/12.5

This sets up 2 offsetting peaks of levodopa overlaying each other. The entacapone helps the mucuna be utilised better.

11am. 1. madopar 50/12.5 + NOW dopa mucuna + 1/2 entacapone

2am. 1 madopar 50/12.5 + NOW dopa mucuna + 1/2 entacapone

5am. 1 madopar 50/12.5

8pm 1/2 madopar 50/12.5

this spreads the levodopa over the beginning of the day then reduces it in the evening when he is producing his own.

He also takes 0.5mg tablet of clonazapam cut into quarters spread over the day and a melatonin at night to sleep plus his supplements:

Hardys DEN with added vitamersx 12, restore gold x 16, 1000mg b1 vitacost, 25 mg b2 dissolved in a bottle of water sipped on over the day, fish oil x2 hempseed oil x2, krill oilx1, pantethine double strength 600mg, ubiquinol 100mg, coq10 100mg, lithium orotate 5 mg, l-glutathione reduced 500mg, biotin 1000mcg, liposomal vitaminc, lutein&zeaxathin, citicoline 250mg.

Supplements